Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.

Abstract

Local adaptations within species are often governed by several interacting genes scattered throughout the genome. Single-locus models of selection cannot explain the maintenance of such complex variation because recombination separates co-adapted alleles. Here we report a previously unrecognized type of intraspecific multi-locus genetic variation that has been maintained over a vast period. The galactose (GAL) utilization gene network of Saccharomyces kudriavzevii, a relative of brewer's yeast, exists in two distinct states: a functional gene network in Portuguese strains and, in Japanese strains, a non-functional gene network of allelic pseudogenes. Genome sequencing of all available S. kudriavzevii strains revealed that none of the functional GAL genes were acquired from other species. Rather, these polymorphisms have been maintained for nearly the entire history of the species, despite more recent gene flow genome-wide. Experimental evidence suggests that inactivation of the GAL3 and GAL80 regulatory genes facilitated the origin and long-term maintenance of the two gene network states. This striking example of a balanced unlinked gene network polymorphism introduces a remarkable type of intraspecific variation that may be widespread.

Regulatory upheaval and the origin and maintenance of the GAL polymorphisms

Key changes in the Saccharomyces GAL gene network, including the origin of Gal− (red) and Gal+ (blue) populations of S. kudriavzevii with some gene flow between them (gradient); the order of some events is uncertain (a). Model showing population-specific variation (light red or blue) arising as mutations and the elimination of variation from most of the genome (YXL#) during gene flow (two-headed arrows) (b). Note that once inactivating mutations (dark red with asterisks) formed GAL pseudogenes, gene flow was prevented within and reduced at linked sequences, resulting in the accumulation of lineage-specific variation at the GAL loci (GAL#).